Hepatitis C (HCV) belongs to the Flaviviridae family of positive-sense, single-stranded RNA viruses. The HCV genome encodes a protein having 3000 amino acid residues that is processed into both structural and nonstructural proteins. HCV infection is a significant global health issue; the World Health Organization estimates that over 170 million people carry the HCV infection, which can ultimately result in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. It has been reported that these complications are responsible for about 10000-20000 deaths annually in the U.S. alone. HCV is one of the leading causes of advanced liver disease and often results in patients requiring liver transplantation. Current therapies for HCV infection rely on combinations of nonspecific antiviral medications, ribavirin, and interferon-α (IFN) (see, for example, a) K. Hanazaki, Curr. Med. Chem.: Anti-Infect. Agents 2003, 2, 103; b) G. M. Lauer, B. D. Walker, N. Engl. J. Med. 2001, 345, 41; c) G. IdNo, A. Bellobuono, Curr. Pharm. Des. 2002, 8, 959; d) A. M. Di Bisceglie, J. McHutchison, C. M. Rice, Hepatology 2002, 35, 224; e) C. E. Samuel, Clin. Microbial. Rev. 2001, 14, 778; the foregoing publication, and each additional publication cited herein, is incorporated herein by reference). Not only do such treatment regimens reportedly cause undesirable side effects such as leucopenia, thrombocytopenia, and hemolytic anemia, but it has been estimated that only about 40% of patients achieve a sustained viral response (see, for example, Gordon & Keller, J. Med. Chem. 2005, 48, 1; Tan et al., Nat. Rev. Drug Discovery 2002, 1, 867). Thus, treatments for HC represent an unmet medical need, especially treatments that are more effective and/or less toxic.
It has been discovered herein that perhydro pyrrolopyridines are active antiviral agents. In particular, it has been discovered herein that perhydro pyrrolopyridines are active against HCV infections.
In one illustrative embodiment, described herein are substituted perhydro pyrrolopyridines that are useful for the treatment of viral diseases including HCV. In another embodiment, described herein are pharmaceutical compositions comprising the substituted perhydro pyrrolopyridines that are useful for the treatment of viral diseases including HCV. Illustratively, the compositions include one or more carriers, diluents, or excipients, or a combination thereof.
In another embodiment, described herein are methods for treating viral diseases including HCV, where the methods include administering the substituted perhydro pyrrolopyridines and/or the pharmaceutical compositions including the substituted perhydro pyrrolopyridines. In another embodiment, described herein is the use of one or more of the substituted perhydro pyrrolopyridines and/or the pharmaceutical compositions including the substituted perhydro pyrrolopyridines in the manufacture of a medicament for treating a patient having a viral disease. Illustratively, the viral disease is hepatitis C.